tetano
Editor, Senior Moderator
J Immunol. 2013 Jul 5. [Epub ahead of print]
Linezolid Decreases Susceptibility to Secondary Bacterial Pneumonia Postinfluenza Infection in Mice Through its Effects on IFN-γ
Breslow-Deckman JM, Mattingly CM, Birket SE, Hoskins SN, Ho TN, Garvy BA, Feola DJ.
Source
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;
Abstract
Influenza infection predisposes patients to secondary bacterial pneumonia that contributes significantly to morbidity and mortality. Although this association is well documented, the mechanisms that govern this synergism are poorly understood. A window of hyporesponsiveness following influenza infection has been associated with a substantial increase in local and systemic IFN-γ concentrations. Recent data suggest that the oxazolidinone antibiotic linezolid decreases IFN-γ and TNF-α production in vitro from stimulated PBMCs. We therefore sought to determine whether linezolid would reverse immune hyporesponsiveness after influenza infection in mice through its effects on IFN-γ. In vivo dose-response studies demonstrated that oral linezolid administration sufficiently decreased bronchoalveolar lavage fluid levels of IFN-γ at day 7 postinfluenza infection in a dose-dependent manner. The drug also decreased morbidity as measured by weight loss compared with vehicle-treated controls. When mice were challenged intranasally with Streptococcus pneumoniae 7 d postinfection with influenza, linezolid pretreatment led to decreased IFN-γ and TNF-α production, decreased weight loss, and lower bacterial burdens at 24 h postbacterial infection in comparison with vehicle-treated controls. To determine whether these effects were due to suppression of IFN-γ, linezolid-treated animals were given intranasal instillations of rIFN-γ before challenge with S. pneumoniae. This partially reversed the protective effects observed in the linezolid-treated mice, suggesting that the modulatory effects of linezolid are mediated partially by its ability to blunt IFN-γ production. These results suggest that IFN-γ, and potentially TNF-α, may be useful drug targets for prophylaxis against secondary bacterial pneumonia following influenza infection.
PMID:
23833238
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23833238
Linezolid Decreases Susceptibility to Secondary Bacterial Pneumonia Postinfluenza Infection in Mice Through its Effects on IFN-γ
Breslow-Deckman JM, Mattingly CM, Birket SE, Hoskins SN, Ho TN, Garvy BA, Feola DJ.
Source
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536;
Abstract
Influenza infection predisposes patients to secondary bacterial pneumonia that contributes significantly to morbidity and mortality. Although this association is well documented, the mechanisms that govern this synergism are poorly understood. A window of hyporesponsiveness following influenza infection has been associated with a substantial increase in local and systemic IFN-γ concentrations. Recent data suggest that the oxazolidinone antibiotic linezolid decreases IFN-γ and TNF-α production in vitro from stimulated PBMCs. We therefore sought to determine whether linezolid would reverse immune hyporesponsiveness after influenza infection in mice through its effects on IFN-γ. In vivo dose-response studies demonstrated that oral linezolid administration sufficiently decreased bronchoalveolar lavage fluid levels of IFN-γ at day 7 postinfluenza infection in a dose-dependent manner. The drug also decreased morbidity as measured by weight loss compared with vehicle-treated controls. When mice were challenged intranasally with Streptococcus pneumoniae 7 d postinfection with influenza, linezolid pretreatment led to decreased IFN-γ and TNF-α production, decreased weight loss, and lower bacterial burdens at 24 h postbacterial infection in comparison with vehicle-treated controls. To determine whether these effects were due to suppression of IFN-γ, linezolid-treated animals were given intranasal instillations of rIFN-γ before challenge with S. pneumoniae. This partially reversed the protective effects observed in the linezolid-treated mice, suggesting that the modulatory effects of linezolid are mediated partially by its ability to blunt IFN-γ production. These results suggest that IFN-γ, and potentially TNF-α, may be useful drug targets for prophylaxis against secondary bacterial pneumonia following influenza infection.
PMID:
23833238
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23833238